Understanding how serum lipids change in response to a cardiac event can provide much needed information to guide clinicians’ selection of appropriate lipid-lowering medication. But many clinicians may fail to order tests for serum lipids early after ACS because of the notion that there are clinically significant declines in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) that occur in the days soon after the event, thereby ruling out meaningful interpretation. Now, new data indicate that lipid levels vary little in the 4 days following ACS and that measuring lipid levels early is useful for guiding medical therapy (Journal of the American College of Cardiology 2008; 51:1440-1445).
Early Intervention Is Key
“There’s substantial evidence indicating that if people who are hospitalized for a cardiac event do not receive statins during their hospital stay, then it’s unlikely they will ever start taking these medications,” noted Bertram Pitt, MD, Emeritus Professor of Cardiovascular Medicine at the University of Michigan School of Medicine, Ann Arbor. “There’s also evidence from the MIRACL Trial that early intervention with statins reduces the subsequent cardiac event rate.” The MIRACL (Myocardial Ischemia Reduction with Acute Cholesterol Lowering) Trial involved more than 3,000 patients treated daily with atorvastatin 80 mg, initiated between 24 and 96 hours after hospital admission and maintained for 16 weeks.
In the current study, Pitt and his colleagues prospectively examined serum lipid parameters among 507 patients hospitalized for an ACS and not receiving treatment with statins. All patients were enrolled in the Limiting UNdertreatment of lipids in ACS with Rosuvastatin—LUNAR—trial, a prospective, randomized, open-label, three-arm, parallel group, 12-week study to compare the efficacy of rosuvastatin 20 mg and 40 mg with atorvastatin 80 mg in lowering LDL-C over 6-12 weeks of once daily therapy. In the new study, Pitt and his colleagues determined serum lipids on days 1, 2 and 4 after the onset of the cardiac event, with direct and indirect assessments of LDL-C. Clinicians placed patients in one of three categories: STEMI, non-STEMI, or unstable angina.
No Clinically Meaningful Changes
The researchers found that LDL-C levels decreased from an average of 136.2 mg/dL to 133.5 mg/dL during the 24-hour period immediately following hospital admission. During the next 2 days, levels increased to an average of 141.8 mg/dL. These changes did not appear to be clinically meaningful, the scientists reported. They observed these changes in the overall study population, as well as in each of the three ACS subgroups.
“The data show that there was relatively little change in any of the parameters during the first four days after admission for an ACS,” noted Pitt. This suggests that LDL-C determinations made in the hospital are reliable and can form the basis for initiating lipid-lowering therapy early, rather than waiting for weeks or even months.”
But the notion of evaluating lipids and lipoproteins in the hospital goes beyond instituting inpatient lipid-lowering therapy, noted Michael Miller, MD, Associate Professor of Medicine, Epidemiology, and Preventive Medicine and Director of the Center for Preventive Cardiology at the University of Maryland Medical Center in Baltimore, Md. In an accompanying editorial he wrote, “Rather, it serves to reinforce the importance of initiating lifestyle and therapeutic measures in-hospital to maximize secondary prevention efforts that include an LDL-C level of less than 70 mg/dL.” (Journal of the American College of Cardiology 2008; 51:1446-1447)
Knowing the extent of the LDL-C level is important as a guide in determining the intensity of treatment, Pitt said. “If the lipid level is high you’d likely want to use a high-dose statin. You can figure out from the baseline LDL how much you need to reduce it to get below 100 mg/dL, or even below 70 mg/dL, which people are now thinking of the new target level.”
Gyorgy Csako, MD, Senior Scientist and Assistant Chief of Clinical Chemistry at the NIH Clinical Center in Bethesda, Md., noted that drug dose also plays an important role in the patient’s overall care. “The LUNAR study compared different dose regimens of two highly effective statins, rosuvastatin and atorvastatin, also known as Crestor and Lipitor, respectively. The study showed that 20-40 mg daily of rosuvastatin has roughly the same effect as 80 mg daily of atorvastatin. This is a big difference in dose and it’s important as the potential for side effects—mostly damage to skeletal muscle—appears to be dose related. Thus, with a lower dose of drug you might be able to reduce the likelihood of having a drug-related adverse reaction.”
Csako, who chairs the AACC’s Lipoproteins and Vascular Diseases Division, noted that there also are other advantages in initiating early therapy to lower lipid levels. “It has been shown in previous studies that patients who have begun such treatment in-hospital seem to better in the long run in terms of compliance compared to those patients who don’t start such therapy until after they have gone home.”
Dr. Pitt has acted as a consultant to Astra Zeneca, Pfizer, Merck, Novartis, Takeda, Synvista, and Nile Therapeutics.